Endocrine Abstracts

Pathogenic ARMC5 variants are the main genetic cause of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) explaining roughly 20% of index cases. These variants found both at germline and somatic level are mostly frameshift and nonsense leading to a loss of its function. ARMC5 acts then, as a tumor suppressor gene but little was initially known on its function. Using an RNAseq analysis on transient zebrafish models of Armc5 up- and d...

Introduction: Osilodrostat and Metyrapone are two CYP11B1 inhibitors used for the treatment of patients with Cushing syndrome. Despite their common suspected mechanism of action, the comparison of serum steroid profiles determined in HPLC-MS/MS in patients treated by either Osilodrostat or Metyrapone for an ACTH-dependent Cushing syndrome identified higher levels of 11-deoxycortisol and androgens in patients treated by Metyrapone than in those treated by Osilodrostat (F. B...

ACTH independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing’s syndrome. Both Phosphodiesterase 11A4 (PDE11A4) mutations and inactivating mutations of armadillo repeat containing 5(ARMC5) have been associated with familial AIMAH. A family with autosomal dominant AIMAH was studied trying to elucidate the involved genetic basis.Methods and results: Adrenal hypercortisolism with giant bilateral AH was diagnosed in three adult me...

Bilateral Adrenal Hyperplasias (BAH) are responsible for approximately 10% of ACTH-independent Cushing syndrome and are classified as either micronodular or macronodular. Whereas Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and isolated Micronodular Adrenal Disease (iMAD) are two types of micronodular hyperplasia, Primary Macronodular Adrenal Hyperplasia (PMAH) is a macronodular BAH. These tumors are classified differently based on clinical, histological and geneti...

Introduction: Bilateral macronodular adrenal disease (BMAD, former PBMAH) is a rare cause of Cushing’s syndrome. The few morphologic descriptions of BMAD mention multinodular hyperplastic adrenal glands composed of clear spongiocytic cells and fewer compact eosinophilic cells without any morphologic variation. The discovery of ARMC5 and KDM1A mutations argues for genetic heterogeneity. The aim of this work was to describe the morphological and immunohist...

ARMC5 is a tumor suppressor gene responsible for 20 to 40% of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) with a function that remains unclear. Based on pathway analysis from RNAseq results obtained on zebrafish models of transient Armc5 up- and down-regulation, we identified transcriptional alterations of several members of SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1) signaling in our models and hypothesized that ARM...

Introduction: Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome. It is characterized by the development of supracentimetric nodules resulting in increased adrenal volume and weight. Its presentation is clinically, radiologically and biologically heterogeneous. Morphological descriptions of PBMAH are rare. Although the initial description highlights that multinodular hyperplastic adrenal glands are made of a majority...

Introduction: Bilateral macronodular adrenal disease (BMAD) is a genetically heterogeneous disease that can be caused by ARMC5 or KDM1A alterations. Indeed, a germline and somatic event leading to a bi-allelic inactivation of ARMC5 or KDM1A are responsible for 20 and 1% of BMAD cases, respectively. Genetic analysis identified three molecular groups: ARMC5, KDM1A and no genetic cause known to date. Although there is a high h...

In adult mice the adrenal cortex is divided, in two distinct functional zones, outermost zona glomerulosa (ZG) and innermost zona fasciculata (ZF), encapsulated by a thin layer of mesenchymal cells (capsule). The adrenal cortex undergoes constant centripetal cell renewal, reliying on recruitment of progenitors located within an outer cortex niche. Progenitors initially differentiate as ZG cells and undergo lineage conversion to ZF as they move within the cortex. This relies on...

Context: Hypertension is one of the most preventable risk factors for cardiovascular disease and death. Up to 42.1% of non-Hispanic African-American subjects have hypertension. We recently found that germline ARMC5 variants may play a role in primary aldosteronism, particularly in African-Americans.Objective: We investigated a cohort of participants in the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) stud...